Glaucoma is an optic neuropathy that affects over 67 million people worldwide. This condition has broad clinical subtypes ranging from birth to very late in life. The most common form, Primary Open Angle Glaucoma (POAG) has a prevalence of about 1% of white population over 40 years of age. Several genetic loci have been identified for POAG but so far only mutations in Myocilin gene are reported in juvenile-onset and certain other adult-onset cases. Recently, we identified a gene that is primarily involved in a subgroup of Adult-Onset POAG, commonly known as Normal Tension Glaucoma (NTG). This gene that we named Optineurin (OPTN) is mutated in 16.7% of our hereditary NTG families, maps to the GLC1E locus on 10p14, has 13 coding exons and encodes for a 577-amino acids protein (~66-kDa). Our OPTN protein studies showed co-localization with Golgi, secretion into aqueous humor and expression in many ocular and non-ocular tissues. Cloning of both mouse and monkey genes showed very similar patterns of mRNA and protein expression to human OPTN. It has also been shown by other investigators that OPTN interacts with Ad E3-14.7K, Huntingtin, TFIIIA, RAB8 and 2 other unknown kinases. Although existing evidence suggest that OPTN through its interaction with other proteins may be utilizing TNF-a or Fas-Ligand pathways to mediate apoptosis, inflammation or vasoconstriction but, as yet, these is no clear indication on how OPTN mutations lead to either NTG or POAG. Therefore, as an initial step towards understanding the ocular function of this gene and its protein products we propose the followings. 1)-Screen a large number of glaucoma patients for OPTN mutations in order to establish a genotype/phenotype correlation; 2)-Use OPTN as "bait" and search for new interacting proteins by Yeast Two Hybrid System and to identify motifs that are important for OPTN function; 3)-Determine ultracellular localization of OPTN in normal and glaucomatous eyes by immunogold labeling; 4)-Study OPTN distribution in normal and glaucomatous eyes by immunohistochemistry and to determine its potential differential tissue expression patterns; and 5)-Use In Situ hybridization to study developmental expression patterns of Optn in mouse embryos. At the conclusion of this investigation, it is anticipated that our study will provide essential scientific information that one day may contribute to the design of innovative and futuristic drug intervention for this group of optic neuropathies.